IMMUNOTHERAPY SUPPRESSES THE PRODUCTION OF MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR AND AUGMENTS THE PRODUCTION OF IL-8 IN CHILDREN WITH ASTHMA

Background: Histamine-releasing factor consists of a group of cytokine s that can cause basophils or mast cells to release histamine. However , the composition of histamine-releasing factor remains undefined. Obj ective: This study was done to measure the concentrations, in plasma a nd mononuclear cell culture supernatants from children with asthma, of chemokines that are known to contribute to histamine-releasing factor activity. Results: Plasma and mononuclear cell culture supernatants w ere obtained from 25 children newly diagnosed with asthma, 25 good res ponders to immunotherapy, 23 poor responders, 25 patients with acute a ttacks, and 13 normal subjects. All the patient groups produced, spont aneously and after stimulation with phytohemagglutinin and mite allerg en, greater amounts of monocyte chemotactic and activating factor, mac rophage inflammatory protein-1 alpha, and RANTES (beta chemokines) and IL-8 and growth-related gene alpha (alpha chemokines) than did normal subjects. Successful immunotherapy resulted in decreased production, especially the spontaneous type, of beta chemokines that cause histami ne release and in increased production of alpha chemokines that inhibi t histamine release. Conclusion: Abnormal chemokine production may con tribute to the pathogenesis of bronchial asthma, and restoration of no rmal chemokine production may be used to explain, in part, the clinica l efficacy of immunotherapy.